This invention relates to solid pharmaceutical dosage forms of the sustained-release type and a method of preparing them. More particularly, this invention relates to sustained-release solid dosage forms coated with an aqueous coating dispersion in the absence of an organic solvent and having a releasing time controllable within a wide range.
Various methods have been proposed for the preparation of sustained-release pharmaceutical dosage forms. For example the dosage forms may be coated with a solution of ethyl cellulose and hydroxypropylmethyl cellulose mixed in a certain ratio in an organic solvent to prolong the disintegration time. Another example is where granules of active ingredients are first made, the granules are then divided into a plurality of groups, each of the groups is coated with an organic solvent solution of cellulose acetate phthalate and polyethylene oxide in a ratio different for each of the respective groups to provide a different disintegration time for each group, the thus coated granules are combined from the individual groups in certain proportions, and the combined granules are encapsulated in hard gelatine capsules.
The disadvantage of these prior art methods is the use of organic solvents to make a coating solution which not only is uneconomical but is also susceptible to explosion or fire and contributes to the pollution of the air and the working environment, when the organic solvents are subject to evaporation.
Apart from the above-described prior art techniques, it is known that organopolysiloxanes of a relatively low viscosity or molecular weight, such as, dimethyl silicone fluids, can be used in the preparation of pharmaceutical tablets. In this case, small amounts of the relatively low viscosity organopolysiloxane fluids that are incapable of forming films are added to the tablet-coating solutions which use an organic solvent. This provides a sufficient slipperiness to the surface of the tablets in the coating process as well as a good gloss and slipperiness to the coated finished surfaces. No attempts have been made to use such organopolysiloxane fluids for the purpose of forming films on the surfaces of tablets non especially, for providing the coated tablets with a sustained release property, in which the organopolysiloxane fluids are used in an aqueous dispersion.
The inventors of this invention, noticing the that orally administered organopolysiloxanes produce no adverse effects to the human body and that films of an organopolysiloxane can afford an excellent permeability to low molecular weight materials, have researched on the preparation of pharmaceutical solid dosage forms which should have a satisfactorily sustained release property. During the course of this research work, the inventors initially attempted to coat tablets and granules with an aqueous emulsion of an organopolysiloxane having a sufficient film-formable high molecular weight. This attempt failed due to to the individual tablets or granules becoming too sticky during the coating operation and having too long release time. However, as a result of their further investigation the inventors have discovered that such undesirable stickines and too long release time could be overcome by the inclusion of a water-soluble cellulose derivative to the coating aqueous emulsion. The inventors have also found that the finished product has the excellent property of sustained release of the active ingredients.